Search results for "RATS"
showing 10 items of 3537 documents
Membrane protein oxidation determines neuronal degeneration
2015
Oxidative stress is an early hallmark in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. However, the critical biochemical effector mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In screening various peroxides and potential substrates of oxidation for their effect on neuronal survival, we observed that intramembrane compounds were significantly more active than aqueous or amphiphilic compounds. To better understand this result, we synthesized a series of competitive and site-specific membrane protein oxidation inhibitors termed aminoacyllipids, whose structures were designed on the basis of amino acids frequently found at the protein-lipi…
Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity
2004
Galantamine is a plant alkaloid that is used in the treatment of Alzheimer's disease. We have studied the effects of galantamine on beta-amyloid-enhanced glutamate toxicity using primary rat cultured cortical neurons. Nicotine and galantamine alone, and in combination, protected neurons against this neurotoxicity. The protection was not blocked by alpha4beta2 nicotinic acetylcholine receptor (nAChR) antagonists, but was partially blocked by alpha7 nAChR antagonists. Galantamine induced phosphorylation of Akt, an effector of phosphatidylinositol 3-kinase (PI3K), while PI3K inhibitors blocked the protective effect and Akt phosphorylation. The antibody FK1, which selectively blocks the alloste…
Differential regulation of apoptosis-associated genes by estrogen receptor alpha in human neuroblastoma cells
2012
Purpose: The neuroendocrinology of female sex hormones is of great interest for a variety of neuropsychiatric disorders. In fact, estrogens and estrogen receptors (ERs) exert neuromodulatory and neuroprotective functions. Here we investigated potential targets of the ER subtype alpha that may mediate neuroprotection and focused on direct modulators and downstream executors of apoptosis. Methods: We employed subclones of human neuroblastoma cells (SK-N-MC) stably transfected with one of the ER subtypes, ERalpha or ERbeta. Differences between the cell lines regarding the mRNA expression levels were examined by qPCR, changes on protein levels were examined by Western Blot and immunocytochemist…
Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging
1993
This article features a novel technique for measuring the spatial distribution of metabolites, such as ATP, glucose, and lactate, in rapidly frozen tissue. Concentration values are obtained in absolute terms and with a spatial resolution of single-cell dimension. The method is based on enzymatic reactions that link the metabolite of interest to luciferase with subsequent light emission. Using a specific array, cryosections are brought into contact with the enzymes in a well-defined, reproducible way inducing a distribution of light across the section with an intensity that is proportional to the metabolite concentration. The emitted light can be visualized through a microscope and an imagin…
Long-chain fatty alcohols from pomace olive oil modulate the release of proinflammatory mediators
2009
Pomace olive oil is a by-product of olive oil extraction that is traditionally produced and consumed in Spain. The nonglyceride matter of this oil is a good source of interesting minor compounds, like long-chain fatty alcohols, which are present free or as part of waxes. In the present study, long-chain fatty alcohols were isolated from the nonglyceride fraction of pomace olive oil, and the composition was identified and quantified. The major components of long-chain fatty alcohols were tetracosanol, hexacosanol and octacosanol. We investigated the ability of long-chain fatty alcohols from pomace olive oil to inhibit the release of different proinflammatory mediators in vitro by cells invol…
Down-regulation of nuclear binding activities of OXBOX-REBOX transcription factors during cellular senescence.
1996
Functional capacity of mitochondria declines during aging and this impairment may have a major role in aging process. Several observations indicate that transcriptional efficiency is reduced during aging. Our purpose was to find out whether aging and cellular senescence affect the nuclear binding activities of transcription factors which bind to OXBOX-REBOX sequence present in promoter regions of numerous nuclear genes encoding mitochondrial proteins. These factors regulate and coordinate the expression of mitochondrial proteins. We observed a strong down-regulation in the nuclear binding activities of OXBOX-REBOX factors in replicatively senesced human WI-38 and IMR-90 fibroblasts. On the …
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia
2018
Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat …
Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture
2001
Oxygen consumption, glucose, lactate, and ATP concentrations, as well as glucose and lactate turnover rates, have been studied in a three-dimensional carcinogenesis model of differently transformed rat embryo fibroblasts (spontaneously immortalized Rat1 and myc-transfected M1, and the ras-transfected, tumorigenic descendants Rat1-T1 and MR1) to determine metabolic alterations that accompany tumorigenic conversion. Various bioluminescence techniques, thymidine labeling, measurement of[Formula: see text] distributions with microelectrodes, and determination of cellular oxygen uptake rates (Q˙[Formula: see text]) have been applied. In the ras-transfected, tumorigenic spheroid types, the size d…
Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors.
2014
Background: Cerebrospinal fluid (CSF) is in contact with brain parenchyma and ventricles, and its composition might influence the cellular physiology of oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple sclerosis (MS) disease pathogenesis. Objective: To identify the transcriptional changes that distinguish the transcriptional response induced in proliferating rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) patients and other neurological controls. Methods: We performed gene microarray analysis of OPCs exposed to CSF from neurological controls, or definitive RRMS or PPMS disease course. R…
Cellular physiology of the neonatal rat cerebral cortex.
2003
The early development of the cerebral cortex is characterized by neurogenesis, neuronal migration, cellular differentiation and programmed cell death. Cajal-Retzius cells, developing cortical plate neurons and subplate cells form a transient synaptic circuit which may serve as a template for the formation of cortical layers and columns. These three neuronal cell types show distinct electrophysiological properties and synaptic inputs. Endogenous or exogenous harmful disturbances during this developmental period may lead to the preservation of early cortical circuits, which may act as trigger zones for the initiation of pathophysiological activity.